Dihydrotestosterone formation (5 alpha-reductase activity) in cultured human skin fibroblasts

Abstract

Testosterone secreted from the testis is converted to dihydrotestosterone (DHT) in target tissues by 5 alpha-reductase and DHT exerts its action on the nucleus. Since skin is one of the target tissues of androgen we established a system for culturing human skin fibroblasts, and we investigated the conversion of testosterone to DHT in genital and nongenital skin fibroblasts obtained from males as well as from females. In our system, fibroblasts were incubated with 0.1 microM 1, 2-3H testosterone, and labeled metabolites were separated by thin layer chromatography. DHT formation was linear for 6 hours and the rate of DHT formation correlated with the growth phase of the fibroblasts. In the course of serial subculture, DHT formation did not change between the 3rd and 10th subculture in four cell strains. DHT formation in nongenital skin fibroblasts did not differ significantly between males and females. Fibroblasts obtained from male genital skin produced significantly greater amounts of DHT than those from male or female nongenital skin. Furthermore, DHT formation in genital skin fibroblasts did not differ between normal males and hypogonadal males. These data suggest that genital skin is the target tissue where testosterone strongly converts to DHT and the difference of male secondary sexual characteristic appearance between males and females may not depend on the sensitivity of the target tissues to androgen but on the secretion rate of androgen.